Histological features of osteoarthritic canine cartilage after prolonged administration of carprofen^[*]

Summary

The objective of this study was to determine whether the non-steroidal anti-inflammatory drug (NSAID) carprofen causes adverse histological changes to cartilage after prolonged administration for treatment of naturally acquired osteoarthritis.

Dogs diagnosed with cranial cruciate ligament rupture and secondary osteoarthritis of their stifle joints were divided into two groups: those who had received a standard dose of carprofen for a minimum of four weeks and those who had not received a NSAID for a minimum of one month. Cartilage from the intercondylar notch was obtained when the patients underwent surgical procedures to stabilize the stifle joint. The samples were processed and evaluated for histological differences using haematoxylin and eosin and safranin-O-fast green-iron haematoxylin stains and were graded according to a Mankin scale (graded 0-14) for osteoarthritis.

The histopathological findings were variable and included loss of matrix staining, irregularities to the cartilage surface, matrix fragmentation, chondrocyte clustering, matrix degeneration and vascular and synovial invasion (pannus) and were not specific to either group. There was not any significant difference between study groups (p = 0.2721) according to the Wilcoxan rank sum test.

Keywords

Carprofen - osteoarthritis - cartilage - non-steroidal antiinflammatory drugs

^* Work supported by a gift from Pfizer Pharmaceuticals.

• References

• 1 Anderson CC, Cook JL, Kreeger JM. et al. In vitro effects of glucosamine and acetylsalicylate on canine chondrocytes in three-dimensional culture. Am J Vet Res 1999; 60: 1546-51.
• 2 Armstrong S, Lees P. Effects of r and s enantiomers and a racemic mixture of carprofen on the production and release of proteoglycan and prostaglandin e2 from equine chondrocytes and cartilage explants. Am J Vet Res 1999; 60: 98-104.
• 3 Benton HP, Vasseur PB, Broderick-Villa GA. et al. Effect of carprofen on sulfated glycosaminoglycan metabolism, protein synthesis, and prostaglandin release by cultured osteoarthritic canine chondrocytes. Am J Vet Res 1997; 58: 286-92.
• 4 Brandt KD. Effects of nonsteroidal anti-inflammatory drugs on chondrocyte metabolism in vitro and in vivo. Am J Med 1987; 83: 29-34.
• 5 Brandt KD, Albrecht M. Effect of naproxen sodium on the net synthesis of glycosaminoglycans and protein by normal canine articular cartilage in-vitro. J Pharm Pharmacol 1990; 42: 738-40.
• 6 Brandt KD, Albrecht ME, Kalasinski LA. Effects of tiaprofenic acid on the concentration and metabolism of proteoglycans in normal and degenerating canine articular cartilage. J Clin Pharmacol 1990; 30: 808-14.
• 7 Dassler CL, Vasseur PB. Concentration of carprofen in synovial fluid from stifle joints with and without osteoarthritis. Veterinary Surgery 1999; 28: 391 (abstract).
• 8 Fernandes JC, Caron JP, Martel-Pelletier J. et al. Effects of tenidap on the progression of osteoarthritic lesions in a canine experimental model. Suppression of metalloprotease and interleukin-1 activity. Arthritis Rheum 1997; 40: 284-94.
• 9 Fernandes JC, Martel-Pelletier J, Jovanovic D. et al. The effects of tenidap on canine experimental osteoarthritis: Ii. Study of the expression of collagenase-1 and interleukin 1beta by in situ hybridization. J Rheumatol 1998; 25: 951-8.
• 10 Fernandes JC, Martel-Pelletier J, Otterness IG. et al. Effects of tenidap on canine experimental osteoarthritis. I. Morphologic and metalloprotease analysis. Arthritis Rheum 1995; 38: 1290-303.
• 11 Fox SM, Johnston SA. Use of carprofen for the treatment of pain and inflammation in dogs. J Am Vet Med Assoc 1997; 210: 1493-8.
• 12 Frean SP, Abraham LA, Lees P. In vitro stimulation of equine articular cartilage proteoglycan synthesis by hyaluronan and carprofen. Res Vet Sci 1999; 67: 183-90.
• 13 Henrotin Y, Reginster JY. In-vitro differences among nonsteroidal antiinflammatory drugs in their activities related to osteoarthritis pathophysiology. Osteoarthritis Cartilage 1999; 07: 355-7.
• 14 Holtsinger RH, Parker RB, Beale BS. et al. The therapeutic efficacy of carprofen (rimadyl-v) in 209 clinical cases of canine degenerative joint disease. Vet Comp Orthop Traumatol 1992; 05: 140-4.
• 15 Howell DS, Pita JC, Muller FJ. et al. Treatment of osteoarthritis with tiaprofenic acid: Biochemical and histological protection against cartilage breakdown in the pond-nuki canine model. J Rheumatol 1991; Suppl 27: 138-42.
• 16 Johnston SA, Budsberg SC. Nonsteroidal antiinflammatory drugs and corticosteroids for the management of canine osteoarthritis. Vet Clin North Am Small Anim Pract 1997; 27: 841-62.
• 17 Johnston SA, Fox SM. Mechanisms of action of anti-inflammatory medications used for the treatment of osteoarthritis. J Am Vet Med Assoc 1997; 210: 1486-92.
• 18 Mankin HJ, Dorfman H, Lippiello L. et al. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. Ii. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am 1971; 53: 523-37.
• 19 Mohr W, Kirkpatrick CJ, Wildfeuer A. et al. Effect of piroxicam on structure and function of joint cartilage. Inflammation 1984; 08 Suppl: S139-54.
• 20 Muir H, Carney SL, Hall LG. Effects of tiaprofenic acid and other nsaids on proteoglycan metabolism in articular cartilage explants. Drugs 1988; 35: 15-23.
• 21 Palmoski MJ, Brandt KD. Aspirin aggravates the degeneration of canine joint cartilage caused by immobilization. Arthritis Rheum 1982; 25: 1333-42.
• 22 Palmoski MJ, Brandt KD. Effect of salicylate on proteoglycan metabolism in normal canine articular cartilage in vitro. Arthritis Rheum 1979; 22: 746-54.
• 23 Palmoski MJ, Brandt KD. Effects of some nonsteroidal antiinflammatory drugs on proteoglycan metabolism and organization in canine articular cartilage. Arthritis Rheum 1980; 23: 1010-20.
• 24 Palmoski MJ, Brandt KD. In vivo effect of aspirin on canine osteoarthritic cartilage. Arthritis Rheum 1983; 26: 994-1001.
• 25 Palmoski MJ, Brandt KD. Relationship between matrix proteoglycan content and the effects of salicylate and indomethacin on articular cartilage. Arthritis Rheum 1983; 26: 528-31.
• 26 Pelletier JP, Lajeunesse D, Hilal G. et al. Carprofen reduces the structural changes and the abnormal subchondral bone metabolism of experimental osteoarthritis. Osteoarthritis Cartilage 1999; 07: 327-8.
• 27 Pelletier JP, Lajeunesse D, Jovanovic DV. et al. Carprofen simultaneously reduces progression of morphological changes in cartilage and subchondral bone in experimental dog osteoarthritis. J Rheumatol 2000; 27: 2893-902.
• 28 Pelletier JP, Martel-Pelletier J. In vivo protective effects of prophylactic treatment with tiaprofenic acid or intraarticular corticosteroids on osteoarthritic lesions in the experimental dog model. J Rheumatol 1991; Suppl 27: 127-30.
• 29 Rainsford KD, Skerry TM, Chindemi P. et al. Effects of the nsaids meloxicam and indomethacin on cartilage proteoglycan synthesis and joint responses to calcium pyrophosphate crystals in dogs. Vet Res Commun 1999; 23: 101-13.
• 30 Ratcliffe A, Azzo W, Saed-Nejad F. et al. In vivo effects of naproxen on composition, proteoglycan metabolism, and matrix metalloproteinase activities in canine articular cartilage. J Orthop Res 1993; 11: 163-71.
• 31 Schneider TA, Budsberg SC. Plasma and synovial concentrations of carprofen in dogs with chronic osteoarthritis. Vet Comp Orthop Traumatol 2001; 14: 19-24.
• 32 Serni U, Mannoni A, Benucci M. Is there preliminary in-vivo evidence for an influence of nonsteroidal antiinflammatory drugs on progression in osteoarthritis? Part ii- evidence from animal models. Osteoarthritis Cartilage 1999; 07: 351-2.
• 33 Slowman-Kovacs SD, Albrecht ME, Brandt KD. Effects of salicylate on chondrocytes from osteoarthritic and contralateral knees of dogs with unilateral anterior cruciate ligament transection. Arthritis Rheum 1989; 32: 486-90.
• 34 Vasseur PB, Johnson AL, Budsberg SC. et al. Randomized, controlled trial of the efficacy of carprofen, a nonsteroidal anti-inflammatory drug, in the treatment of osteoarthritis in dogs. J Am Vet Med Assoc 1995; 206: 807-11.